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Stephen V Liu, MD

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Sep 11 • 5 tweets • 5 min read

@LauraMezquitaMD

Dr. @LauraMezquitaMD discusses the DESTINY-Lung02 data at #ESMO22

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate (ADC) targeting #HER2 and in DESTINY-Lung01, RR was encouraging at 55% but some concern for toxicity (adjudicated drug-related ILD in 26% of cases). #ESMO22

In DESTINY-Lung02, we have a randomization of pts with #HER2 mt NSCLC (with prior therapy) to the 6.4 mg/kg dose used in DESTINY-Lung01 or a lower, 5.4 mg/kg dose. RR higher at 5.4 (due to maintained intensity from less tox? or imbalance in baseline characteristics?) #ESMO22

Key toxicity is interstitial lung disease (ILD) and in DESTINY-Lung02, ILD rate lower at the 5.4mg/kg dose (6% overall, 1% G3) than the 6.4mg/kg dose (14% - also lower than the 26% seen in DESTINY-Lung01). Quicker onset at higher dose #ESMO22

@IASLC

For more, listen to this episode of the @IASLC podcast, Lung Cancer Considered, to hear Drs. @JulienMazieres and @LudaBazhenovaMD discuss trastuzumab deruxtecan (T-DXd) in #HER2 NSCLC (references older dose, not this new data). #ESMO22

iaslc.org/iaslc-news/lun…

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Stephen V Liu, MD

@StephenVLiu

Sep 11

Dr. Silvia Novello presents 5y update on KEYNOTE 407 (platinum plus tax and +/- pembrolizumab for 1L squamous NSCLC #ESMO22

With longer follow up, OS favors pembrolizumab arm with mOS 17.2 vs 11.6m (OS HR 0.71) in squamous NSCLC. 5y OS rate 18.4% vs 9.7%. PFS benefit (HR 0.62) and higher RR across PDL1 strata. #ESMO22

For patients who complete 2y of pembrolizumab, 3y OS rate (after completing 2y pembro) was 70% - though not all of those patients are cured (44% were alive without PD or subsequent therapy). #ESMO22

Read 4 tweets

Stephen V Liu, MD

@StephenVLiu

Sep 11

@marinagarassino

Dr. @marinagarassino presents 5-year efficacy and safety update of KEYNOTE-189 (1L carboplatin plus pemetrexed +- pembrolizumab in non-squamous NSCLC) #ESMO22

KEYNOTE 189 is our SOC and has shown a consistent benefit including improving OS even with a crossover rate of 57%. #ESMO22

KEYNOTE 189 shows sustained OS benefit with longer follow up and a 5y OS rate of 18.4% with an OS HR of 0.60. Better PFS and OS also observed. Benefit across PDL1 strata. No new safety signals . #ESMO22

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Stephen V Liu, MD

@StephenVLiu

Sep 11

Dr. Baohui Han presents SUNRISE: randomized phase II study of sintilimab (PD1) and anlotinib (anti-angiogenic TKI) in metastatic NSCLC. #ESMO22

Study design here shows randomization to first-line sintilimab + anlotinib or chemo (with sintilimab at progression). Some concerns about randomization to chemotherapy without immunotherapy in a modern day study. #ESMO22

Baseline characteristics show a fairly high proportion of never smokers. SUNRISE excluded EGFR, ALK, and ROS1 - would like details on testing methods and presence of other drivers. More pts with brain and liver metastases in the sintilimab + anlotinib arm. #ESMO22

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Stephen V Liu, MD

@StephenVLiu

Sep 11

Dr. Koichi Goto starts the lung mini oral session with results from DESTINY-Lung02 of the recently approved trastuzumab deruxtecan in #HER2 NSCLC #ESMO22

DESTINY-Lung02 compared two doses of trastuzumab deruxtecan (T-DXd) in #HER2 previously treated NSCLC (5.4 mg/kg vs 6.4 mg/kg): RR 58% and DoR 8.7m at the lower dose compared to 43% at 6.4 mg/kg. #ESMO22

Importantly- interstitial lung disease much less frequent at the 5.4 mg/kg dose (5.9%, only 1 case of G3). This is the FDA approved dose of trastuzumab deruxtecan in #HER2 NSCLC #ESMO22

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Stephen V Liu, MD

@StephenVLiu

Sep 11

@NReguart

Discussant Dr. @NReguart reminds us of the heterogeneity of stage III NSCLC and our teaching has been to determine resectability before treatment. The INCREASE study starts to challenge that. #ESMO22

The difference here is radiation and in T3/T4 NSCLC, local control is so critical. Largely unexplored to date. The INCREASE study explores quad-modality therapy and the results were quite impressive. High pCR rates and seen across PDL1 strata, not just in PDL1 high. #ESMO22

#ESMO22 High G3 TRAE rates but note that use of platinum + etoposide was common and many of these may have been paper toxicities. Any grade pneumonitis only 11% (note radiation dose was usually 50 Gy).

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Stephen V Liu, MD

@StephenVLiu

Sep 11

Dr. Eddie Garon presents data from CANOPY-A - adjuvant canakinumab for resected NSCLC #ESMO22

Canakinumab in the CANTOS study was associated with a reduction in NSCLC incidence. Led to CANOPY-A: large study of adjuvant canakinumab after surgery and chemotherapy for NSCLC. #ESMO22

Adjuvant canakinumab did not improve DFS (HR 0.939). CANOPY-A clearly a negative study. #ESMO22

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